Comparative evaluation of cellular uptake of free and liposomal doxorubicin following short term exposure
Date
2021Author
Zaleskis, Gintaras
Garberytė, Sima
Pavliukevičienė, Božena
Krasko, Jan Aleksander
Skapas, Martynas
Talaikis, Martynas
Darinskas, Adas
Žibutytė, Lavija
Pašukonienė, Vita
Metadata
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Background/Aim: Liposomal Doxorubicin (lipDOX) and free Doxorubicin (DOX) are reported to exhibit similar antitumor efficacy. However, cellular internalization mechanisms of lipDOX are still a subject of controversy. Materials and Methods: Intact and permeabilized cells were exposed for short time to lipDOX and free DOX and drug intracellular content was evaluated by flow cytometry. Then, the antiproliferative capacities of lipDOX and free DOX were compared by the leukocyte nadir test in mice in vivo. Results: The fluorescence increase was 11.2-fold higher in intact cells and 19.7-fold higher in permeabilized cells after exposure to free DOX as compared to lipDOX. Mice injected with DOX showed pronounced antiproliferative activity with a leukocyte count decrease to 2.8±0.65 k/μl (p<0.01) – an effect significantly stronger than that in the lipDOX group. Conclusion: Intact and permeabilized cells internalize free DOX manifold faster than lipDOX. The LipDOX formulation does not induce a remarkable leukocyte nadir effect in vivo.